Cholesterol efflux capacity (CEC) appears to improve atherosclerotic cardiovascular disease (ASCVD) risk prediction—beyond what coronary artery calcium (CAC), family history, and high-sensitivity C-reactive protein (hs-CRP) can provide, according to data published in the Journal of the American College of Cardiology.

As the study authors pointed out, low high-density lipoprotein cholesterol (HDL-C) is considered an important risk factor for ASCVD, but that association may be attenuated.

They enrolled 1972 individuals (mean age: 44 ± 9.2 years; 44% men; 47% African Americans) who were part of the Dallas Heart Study. Fifty-two percent of patients had prevalent CAC. Family history and “premature” family history were also reported in 31% and 10%, respectively, as well as hs-CRP >2 mg/l in 58% of patients.

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The primary end point was a composite of first nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]), or death from CV causes. Nonfatal end points were ascertained and adjudicated by 2 cardiologists who were unaware of the CEC measurements.

A first ASCVD event occurred in 97 patients, which included 28 MIs, 32 strokes, 5 CABGs, 11 PCIs, and 21 CV deaths during a median 9.4 years of follow-up (95% confidence interval [CI]: 9.0-9.8). A decreased risk of ASCVD was observed in those patients with CEC more than the median vs less than the median (3.1% vs 6.7%; P=.0003).

In patients with prevalent CAC (n=1030), those with CEC more than the median vs less than the median also had a decreased risk of ASCVD (5.4% vs 10.5%; P=.003). Patients with family history and elevated hs-CRP saw similar results (5.8% vs 10%; P=.05 and 3.8% vs 7.9%; P=.004, respectively).

CEC remained inversely associated with incident ASCVD without attenuation in a fully adjusted model that accounted for all traditional risk factors, prevalent CAC, family history, elevated hs-CRP (adjusted hazard ratio [HR]: 0.35; 95% CI: 0.23-0.55).

“The ability of CEC to improve risk prediction beyond using CAC, FH [family history], and hs-CRP was assessed using metrics of calibration, discrimination, and reclassification,” researchers wrote. “CEC more than the median vs less than the median improved discrimination indexes as determined by the c-statistic and IDI [integrated discrimination improvement] when added to risk factor-adjusted models, including either prevalent CAC, FH, or elevated hs-CRP.”

They concluded, “Among low-risk individuals, efflux adds to ASCVD risk prediction beyond using CAC, FH, and hs-CRP, which are 3 well-validated and clinically used markers.”

In the future, if standardized assays are developed, CEC may serve as a surrogate marker for evaluating novel therapeutic strategies.


Mody P, Joshi PH, Khera M, Ayers CR, Rohatgi A, et al. Beyond coronary calcification, family history, and C-reactive protein. Cholesterol efflux capacity and cardiovascular risk prediction. J Am Coll Cardiol. 2016;67(21):2480-2487. doi: 10.1016.j.jacc.2016.03.538.